PROJECT SUMMARY This K08 application aims at examining a potential fetal origin of inhibitory control difficulties: in utero exposure to prenatal maternal obesity. This study fills a crucial gap by examining inhibitory control deficits in an intergenerational sample of Puerto Ricans in the US. This community, alongside other Latino populations, has seen an increase in obesity and impulsivity-related disorders such as attention-deficit/hyperactivity disorder (ADHD), yet remains vastly understudied. This five-year K08 application presents a program for research and training that will support the applicant on a path towards becoming an independent investigator, focused on studying the early origins of inhibitory control deficits through an interdisciplinary approach (life course epidemiology, infant neuroimaging, and biostatistics). The training plan builds on the candidate's prior training and experience and capitalizes on an outstanding mentorship team and research environment to foster the development of the candidate's expertise in (1) collection, analysis, and interpretation of infant resting state functional Magnetic Resonance Imaging (fMRI) data; (2) perinatal weight and inflammation and its relationship to fetal neurodevelopment; (3) life course epidemiologic research with ethnic/racial minority populations; (4) phenomenology and assessment of inhibitory control in toddlers; and (5) responsible conduct in scientific research. This project will investigate the influence of high maternal prenatal body mass index (BMI) on frontostrialal connectivity (i.e., circuits implicated in inhibitory control disorders) in offspring infants (Aim #1) and on behavioral assessments of inhibitory control at age 2 (Aim # 2). It is hypothesized that inflammation is a key mediator (i.e. mechanism) by which maternal prenatal BMI leads to disruptions in frontostriatal connectivity in infants and impaired inhibitory control in toddlers. The project will collect prenatal assessments of maternal BMI and inflammation, resting state fMRI data from infants at 2-4 weeks of age, and behavioral and parent report measures of inhibitory control abilities at age 2. Currently, the proposed study participants are enrolled in the NIH Environmental influences on Child Health Outcomes (ECHO) study, which will collect MRI data on 500 infants. Building on this structure, we propose to select a subsample (n=76) of average (BMI=18.5? 24.9 kg m?2; n=38) and obese (BMI?30 kg m?2; n=38) pregnant women and offspring to include in this project. Data yielded from the proposed study will lead to a future R01 application examining offspring's inhibitory control circuits longitudinally. Together, the research and training experiences and expertise developed through this K08 award will support the applicant's transition to research independence and ensure the applicant becomes a leading authority in the prenatal origins of inhibitory control deficits.